Discrete Event Simulation (DES) is nowadays widely used to support decision makers in system analysis and improvement. However, the use of simulation for improving stochastic logistic processes is not common among healthcare providers. The process of improving healthcare systems involves the necessity to deal with trade-off optimal solutions that take into consideration a multiple number of variables and objectives. Complementing DES with Multi-Objective Optimization (SMO) creates a superior base for finding these solutions and in consequence, facilitates the decision-making process. This paper presents how SMO has been applied for system improvement analysis in a Swedish Emergency Department (ED). A significant number of input variables, constraints and objectives were considered when defining the optimization problem. As a result of the project, the decision makers were provided with a range of optimal solutions which reduces considerably the length of stay and waiting times for the ED patients. SMO has proved to be an appropriate technique to support healthcare system design and improvement processes. A key factor for the success of this project has been the involvement and engagement of the stakeholders during the whole process.